The present invention relates to methods and apparatus for collecting, processing and transfusing blood in general and, in particular, to a novel method and apparatus for diluting packed red blood cells contained in a transfusion bag.
Transfusion bags containing packed red blood cells are obtained in the first step of conventional blood processing in which whole blood obtained from a donor is separated into its component parts.
A principal physical characteristic of packed red blood cells which gives rise to the present invention and which is evident during normal transfusions is their high viscosity and corresponding relatively low flow rate in comparison to the flow rate obtained with whole blood.
Whether the low flow rate in a normal transfusion of packed red blood cells is acceptable depends on the nature or character of the therapeutic application or procedure involved. In cases of emergency injuries and operations involving trauma and high volume blood loss, low flow rates are generally unacceptable. In these cases, the packed red blood cells must be diluted or whole blood must be used.
At the present time, using conventional methods and apparatus, the dilution of packed red blood cells is time-consuming and troublesome. Quite frequently, it is wasteful of diluent used for diluting the packed red blood cells. It may also be dangerous to a patient if the diluent used is incorrect in amount or type, as may occur in the excitement of an emergency or operation involving high volume blood loss.
On the other hand, the use of whole blood simply to avoid the time and trouble of diluting packed red blood cells, when only the extra oxygen-carrying capacity of the red blood cells is required, has long been recognized by medical authorities as being wasteful of the non-required blood components. The use of whole blood when it is necessary only for high flow rates is also recognized as being potentially dangerous to a patient, as will be further explained below.
The time and trouble encountered by a physician and the potential danger to a patient and loss of supplies using conventional methods and apparatus for diluting packed red blood cells may be made more clear by means of a simple and brief description of conventional blood collecting, processing and transfusing techniques and apparatus.
Conventionally, whole blood is received from a donor in a relatively small plastic bag having a volume of about 500 cc. In preparation for receiving the whole blood, the bag, commonly called a primary bag, is filled with a small quantity of an anti-coagulent.
Coupled to the primary bag by means of a plurality of hollow tubes, there is provided a number of satellite bags. The primary and satellite bags are interconnected by the tubes in such a manner that no air is admitted to the bags and the component parts of the blood in the course of the blood processing can be transferred from one bag to another with no potential hazard from bacterial contamination. This was not possible in the past when blood was collected, processed and transfused using glass bottles.
In the past, any penetration of the blood containers, as by a needle or the like inserted through the rubber stoppers used for closing the bottles created the potential hazard of bacterial contamination. This resulted in a requirement that the potentially contaminated blood components be used within twenty-four hours. The twenty-four hour restriction insured that a patient's normal biological immunities could handle the bacterial contamination if it occurred.
In the first step of the processing of whole blood into its component parts, a primary bag filled with whole blood and its satellites are placed in a centrifuge. After a predetermined time at a predetermined RPM, the red blood cells and plasma in the whole blood are separated. Thereafter, about 200 cc of the plasma is transferred from the primary bag to a first one of the satellite bags. The other satellite bags are used for the subsequent separation of additional blood components from the plasma, but forming no part of the present invention, the steps involved need not be further explained for an understanding of the present invention. It need only to be understood that the other components are very important for blood component therapy and can be obtained only from existing quantities of whole blood.
After the removal of the 200 cc of plasma from the primary bag, the primary bag is sealed, as by thermal bonding techniques, and separated from the satellite bags for storage in a refrigerator until the red blood cells contained therein are required for a transfusion. At this point, and for obvious reasons, most persons handling the primary bag now call it a transfusion bag. With the plasma removed, the red blood cells are much closer together and, being without their normal supporting medium, plasma, become "packed," hence the designation, packed red blood cells.
Having considered how the packed red blood cells are obtained, consideration may now be given to how they are diluted using conventional methods and apparatus.
When a physician orders packed red blood cells for a transfusion and there is a possibility that a high-volume, high-flow-rate transfusion may be required, an appropriate diluent will normally also be ordered. The orders are generally directed to a local in-house blood service. Alternatively, the blood service may provide the red blood cells while the diluent is obtained from a supply of various types of diluents stored close at hand. This is possible since typical diluents are simply isotonic or slightly hypotonic saline solutions and do not require special storage facilities. Regardless of the source of the diluent, most facilities heretofore stored and supplied the diluent in large, 500-1000 cc glass bottles.
In practice, if the diluting of packed red blood cells is required, a physician typically suspends the diluent bottle from a first rack or hanger and a unit or transfusion bag of packed red blood from another rack or hanger. A tube is then inserted in the diluent bottle and in a port of the transfusion bag. Generally the tube is provided with a needle or the like at one or both of its ends as a fitting to effect the coupling. To prevent reverse flow from the transfusion bag to the diluent bag, the transfusion bag is usually maintained at a position below the diluent bottle.
As may be recalled from the foregoing discussion, the amount of plasma removed from the transfusion bag is typically 200 cc. Accordingly, in the course of diluting the packed red blood cells, it is necessary for the physician to carefully control the amount of diluent used to return the packed red blood cells to the concentration present in whole blood. Since the gravity flow is not usually very turbulent, it is also frequently necessary for the physician or an attendant to agitate the transfusion bag to mix the packed red blood cells and diluent homogeneously.
In many non-emergency cases and in particular in the case of an emergency or an operation involving high-volume blood loss, it can be seen that the time it takes to dilute a transfusion bag, the care that must be exercised to insure that only the proper amount of diluent is added to the bag and the trouble that is involved in having to agitate the bag all tend to make the diluting of packed red blood cells, using conventional methods and diluent bottles, unacceptable. It should also be noted that, unless all of the diluent is used once a diluent bottle has been penetrated, the remaining diluent must be discarded. This is because, as previously discussed, any penetration of a blood or diluent container creates a potential hazard for bacterial contamination requiring that the components and diluent be used immediately.
Another problem with conventional diluting methods and apparatus is that the availability of various types of diluents in the same type of container can give rise, and has not infrequently given rise, in the excitement of an emergency or the like, to the inadvertent use of the wrong diluent.
For the foregoing reasons, and becasue the attending physician is the person who is ultimately responsible for the proper dilution and administration of the blood, blood service personnel and others not under the direct supervision of the physician are not in a position to relieve the physician of the time and trouble associated with the use of conventional methods and apparatus for diluting packed red blood cells.
Turning now to the use of whole blood as a substitute for diluting packed red blood cells, as previously discussed, it has long been recognized as wasteful and potentially dangerous in many, if not a majority of cases. For example, in Volume 212, No. 1 of the Journal of the American Medical Association, dated Apr. 6, 1970, in an article entitled "Whole Blood Use Called Wasteful," it is contended that "component transfusion therapy is better transfusion therapy," and, referring to a then new handbook, it is stated: "The use of whole blood is `shotgun` therapy, wasting valuable components and endangering the patient with the unnecessary burdens of volume, acidosis, electrolytes and antibodies." In the same article, a past president of the American Association of Blood Banks is reported as stating: "Acute blood loss resulting from surgery or trauma is about the only remaining case in which using whole blood remains preferable to components."
In the same article it is stated: "Transfusion of red blood cells (also referred to as concentrated, packed, or enriched red blood cells) rather than whole blood, is generally the best and safest method of fulfilling a patient's need for increased oxygen-carrying capacity. Whether that need results from chronic anemia or acute blood loss, red blood cells, properly prepared, have the same shelf life as whole blood."
In the article, some of the advantages of packed red blood cell transfusions pertinent to the present invention are listed:
(1) The risk from metabolic by-products which accumulate in plasma during storage of whole blood (such as lactic acid, potassium, inorganic phosphate and ammonia) is reduced.
(2) The risk of reactions to allergens and antibodies in plasma is reduced.
(3) The risk of reactions to plasma protein antigens is reduced in multi-transfused recipients.
In summary, the article concludes with the statement that, "it is likely that from 60% to 80% of blood transfusion needs can and should be met by use of red blood cells (rather than whole blood)."
If packed red blood cells were used instead of whole blood, considerably less whole blood would be required to obtain the necessary component parts for specific applications. In spite of this fact, it is reported in the Lancet, Letters to the Editor, Feb. 15, 1969, at page 372, that "The high viscosity of packed red blood cells renders their clinical use very difficult."
Even though the problems associated with the use of conventional methods and apparatus for diluting packed red blood cells was well recognized as far back as early 1969, both the problems and the absence of any adequate solution therefor has persisted until the present invention, as evidenced by a recent article in Transfusion. In an article entitled "Microaggregate Content and Flow Rates of Packed Red Blood Cells," Transfusion, September-October, 1977, pages 484-489, it is reported that: "It is frequently maintained that the flow rate of red blood cells is too slow to be useful during the brisk bleeding that may be encountered at operations."
In addition to the foregoing considerations militating against the use of whole blood as a substitute for properly diluted packed red blood cells, there is the consideration of the amount of whole blood necessary to supply the present needs of both those using blood components and whole blood.
The above quoted estimate of 60-80% of blood optimally being transfused as packed red blood cells is based on their limited use in surgery and trauma for the reasons discussed. If the dilution of packed red blood cells were made convenient and simple, it is likely that virtually all blood transfusions could be achieved using diluted packed red blood cells. This could result in an additional 1,000,000 liters of plasma from whole blood per year in this country, which would substantially reduce or eliminate the need for paid plasma donors.
As the amount of blood and plasma obtained from commercial sources is reduced, the problems associated with hepatitis and other blood-related diseases are likely to also be reduced. Needless to say, the cost of collecting the blood will, of course, be reduced substantially.